Dietary Nucleotides Promote Neonatal Rat Microbiota–Gut–Brain Axis Development by Affecting Gut Microbiota Composition and Metabolic Function

A variety of active factors in milk and foods have been proven to serve as microbial nutrients that regulate the formation of early gut microbiota (GM), thereby ensuring the healthy development of infants. This study demonstrated that dietary nucleotides (NTs), one of the main nitrogen-containing substances in human milk, promoted the neurodevelopment of neonatal rats and the expression of Sox2, Dcx, Tuj1, and NeuN in the prefrontal cortex and hippocampus, but had no significant regulatory effects in the striatum. 16s rRNA sequencing and metabolomics of the colon contents of neonatal rats at different developmental stages showed that the early intake of NTs promoted an increase in the abundance of beneficial microorganisms related to neurodevelopment, digestion, and gut absorption, such as g_Romboutsia and g_Akkermansia. Changes in the ability of the GM to regulate folate synthesis, riboflavin metabolism, and other processes were also observed. Further analysis revealed significant correlations between the level of characteristic metabolites, namely, trans-3-indoleacrylic acid, urocanic acid, inosine, and adenosine, in the gut with neurodevelopment and characteristic GM components. These findings suggest that NTs in milk may affect neurodevelopment and maturation in early life by regulating the GM composition-gut-brain axis.